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Ontario Provincial Police say the crash occurred on Indian Line Road.
Emergency personnel including Norfolk OPP, Six Nations Police Service, Norfolk County Paramedic Services and Norfolk County firefighters responded to the scene at about 5:45 p.m.
The driver of the ATV was transported to hospital for treatment of what police describe as serious but non-life-threatening injuries.
The driver of the other vehicle was not injured.
Indian Line Road between Villa Nova Road and Concession 2 Townsend were closed for several hours during the investigation.
Anyone with information about the collision is asked to contact the Norfolk County OPP Detachment at 1-888-310-1122. Those wishing to remain anonymous can call Crime Stoppers at 1-800-222-8477 or leave an anonymous online tip at www.helpsolvecrime.com.